Diisopropylethylamine → HCID 178502371, compound

HRID 1776044Notes

Reaction equation

HRID 1776044 reaction equation
OC(C(F)(F)F)=O.[CH3:8][O:9][C:10]([NH:12][C@@H:13]([CH:46]([CH3:48])[CH3:47])[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21]1[NH:22][CH:23]=[C:24]([C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][C:35]([C:38]([OH:40])=O)=[CH:34][C:33]=3[O:41][C:42]([F:45])([F:44])[F:43])=[CH:28][CH:27]=2)[N:25]=1)=[O:15])=[O:11].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:73]([O:77][C:78]([N:80]1[CH2:85][CH2:84][N:83]([C:86]2[CH:91]=[CH:90][C:89]([NH2:92])=[CH:88][N:87]=2)[C@H:82]([CH3:93])[CH2:81]1)=[O:79])([CH3:76])([CH3:75])[CH3:74].C(N(CC)C(C)C)(C)C>CC(N(C)C)=O>[C:73]([O:77][C:78]([N:80]1[CH2:85][CH2:84][N:83]([C:86]2[CH:91]=[CH:90][C:89]([NH:92][C:38]([C:35]3[CH:36]=[CH:37][C:32]([C:29]4[CH:28]=[CH:27][C:26]([C:24]5[N:25]=[C:21]([C@@H:17]6[CH2:18][CH2:19][CH2:20][N:16]6[C:14](=[O:15])[C@@H:13]([NH:12][C:10]([O:9][CH3:8])=[O:11])[CH:46]([CH3:48])[CH3:47])[NH:22][CH:23]=5)=[CH:31][CH:30]=4)=[C:33]([O:41][C:42]([F:44])([F:45])[F:43])[CH:34]=3)=[O:40])=[CH:88][N:87]=2)[C@H:82]([CH3:93])[CH2:81]1)=[O:79])([CH3:76])([CH3:74])[CH3:75]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67495583HCID 67495583, compoundHCID 178502372HCID 178502372, compound

Product 1

HCID 178502371HCID 178502371, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

A mixture of 4′-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-2-trifluoromethoxy-biphenyl-4-carboxylic acid TFA (600 mg, 0.9 mmol) and HATU (364 mg, 0.96 mmol) in DMA (8 mL) was stirred at RT for 15 min and then 0.5 M (R)-4-(5-amino-pyridin-2-yl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester in DMA (1.7 mL) was added followed by N,N-diisopropylethylamine (0.76 mL, 4.36 mmol). The resulting mixture was heated at 55° C. overnight, washed with EtOAc (100 mL) and water (25 mL). The organic layer was washed again with water and then with brine, dried over sodium sulfate, filtered, and concentrated to yield a dark reddish oil which was purified by silica gel chromatography (40 g silica column, 0-80% hexane:EtOAc) to provide (R)-4-{5-[(4′-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-2-trifluoromethoxy-biphenyl-4-carbonyl)-amino]-pyridin-2-yl}-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (646 mg) as a light brownish solid.

Workup

  1. temperatureThe resulting mixture was heated at 55° C. overnight
  2. washwashed with EtOAc (100 mL) and water (25 mL)
  3. washThe organic layer was washed again with water
  4. dry with materialwith brine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a dark reddish oil which
  8. customwas purified by silica gel chromatography (40 g silica column, 0-80% hexane:EtOAc)

Sources & evidence

ORD record
ord-1e5b9d616baf4e298580827d3734b83f
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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